Structures of RNA polymerase-antibiotic complexes.

Current Opinion in Structural Biology
Mary X HoRichard H Ebright

Abstract

Inhibition of bacterial RNA polymerase (RNAP) is an established strategy for antituberculosis therapy and broad-spectrum antibacterial therapy. Crystal structures of RNAP-inhibitor complexes are available for four classes of antibiotics: rifamycins, sorangicin, streptolydigin, and myxopyronin. The structures define three different targets, and three different mechanisms, for inhibition of bacterial RNAP: (1) rifamycins and sorangicin bind near the RNAP active center and block extension of RNA products; (2) streptolydigin interacts with a target that overlaps the RNAP active center and inhibits conformational cycling of the RNAP active center; and (3) myxopyronin interacts with a target remote from the RNAP active center and functions by interfering with opening of the RNAP active-center cleft to permit entry and unwinding of DNA and/or by interfering with interactions between RNAP and the DNA template strand. The structures enable construction of homology models of pathogen RNAP-antibiotic complexes, enable in silico screening for new antibacterial agents, and enable rational design of improved antibacterial agents.

References

Jan 1, 1977·Topics in Current Chemistry·W Wehrli
Jan 1, 1990·The Journal of Antibiotics·G RömmeleW Wehrli
Feb 1, 1985·The Journal of Antibiotics·H IrschikH Reichenbach
Jul 1, 1969·Journal of Bacteriology·C SiddhikolB Weisblum
Apr 14, 1971·Nature: New Biology·G CassaniL Gold
Jan 1, 1983·Molecular & General Genetics : MGG·Y A OvchinnikovR B Khesin
Aug 1, 1995·The Journal of Antibiotics·H IrschikH Reichenbach
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Jan 25, 2000·Tubercle and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·S Ramaswamy, J M Musser
Oct 19, 2000·Antimicrobial Agents and Chemotherapy·A O'NeillI Chopra
Feb 13, 2002·Current Opinion in Structural Biology·Patrick Cramer
May 10, 2002·Nature·Dmitry G VassylyevShigeyuki Yokoyama
May 6, 2004·Trends in Biochemical Sciences·Seth A Darst
Oct 16, 2004·Bioorganic & Medicinal Chemistry Letters·Thomas DoundoulakisKlaus B Simonsen
Feb 11, 2005·Chemical Reviews·Heinz G Floss, Tin-Wein Yu
Sep 17, 2005·Molecular Cell·Dmitry TemiakovDmitry G Vassylyev
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Min-Yi Shen, Andrej Sali
Mar 3, 2007·Drug Discovery Today·Philippe Villain-GuillotJean-Paul Leonetti
Jun 22, 2007·Nature·Dmitry G VassylyevIrina Artsimovitch
Jun 22, 2007·Nature·Dmitry G VassylyevRobert Landick
Sep 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Andrey FeklistovRichard H Ebright
Oct 24, 2008·Nature·Georgiy A BelogurovDmitry G Vassylyev
Oct 30, 2008·Cell·Jayanta MukhopadhyayRichard H Ebright
Jun 2, 2009·Current Opinion in Structural Biology·Florian BruecknerPatrick Cramer
Aug 12, 2009·Journal of the American Chemical Society·Amos B SmithRichard J Fox

❮ Previous
Next ❯

Citations

Mar 7, 2014·Nature Communications·Anssi M MalinenGeorgiy A Belogurov
Oct 2, 2013·International Journal of Medical Microbiology : IJMM·Till F SchäberleKenneth Pfarr
Jun 13, 2013·The Journal of Antibiotics·Christopher T Walsh, Timothy A Wencewicz
Sep 1, 2014·European Journal of Medicinal Chemistry·Giovanna PoceMariangela Biava
Apr 18, 2013·Tuberculosis·Alexander SpeerMichael Niederweis
Mar 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Scott R Kennedy, Dorothy A Erie
Jul 1, 2011·Journal of the American Chemical Society·Sergey V ProninSergey A Kozmin
Sep 26, 2012·Antimicrobial Agents and Chemotherapy·Aashish SrivastavaRichard H Ebright
Jan 22, 2013·Antimicrobial Agents and Chemotherapy·Yukinori TanakaKozo Ochi
Feb 8, 2013·The Journal of Biological Chemistry·Katsuhiko S Murakami
Sep 12, 2012·Nucleic Acids Research·Simone C WieslerMartin Buck
May 30, 2015·Biomolecules·Emily F RuffIrina Artsimovitch
Nov 22, 2011·European Journal of Medicinal Chemistry·Ricardo FigueiredoMaria do Céu Costa
Aug 25, 2011·Current Opinion in Microbiology·Aashish SrivastavaRichard H Ebright
Mar 20, 2010·Tuberculosis·Paul A AristoffH D Showalter
May 11, 2011·Chemical Biology & Drug Design·Chloe A HollowayMuhammad Yaqoob
Apr 9, 2011·EMBO Reports·Charles S McHenry
Jul 16, 2015·Pharmaceutical Patent Analyst·Jozef Stec, Ehab A Abourashed
Jul 16, 2010·FEMS Microbiology Reviews·Tamaswati GhoshXiaodong Zhang
May 27, 2014·Frontiers in Pharmacology·Santi M MandalOctavio L Franco
Mar 23, 2017·ACS Chemical Biology·Scott S WalkerKatherine Young
Jul 7, 2017·Medicinal Research Reviews·Matilde E LleonartAlex Lyakhovich
Apr 6, 2018·Clinical Nurse Specialist CNS·Patricia Anne O'Malley
Jul 6, 2014·Angewandte Chemie·Peter M WrightAndrew G Myers
Aug 13, 2014·Chemistry : a European Journal·Wufeng TangEvgeny V Prusov
Jan 15, 2016·Microbiology and Molecular Biology Reviews : MMBR·Cong MaPeter J Lewis
Nov 23, 2018·Journal of Industrial Microbiology & Biotechnology·Sonia I MaffioliStefano Donadio
May 21, 2014·Natural Product Reports·Till F SchäberleGabriele M König
Sep 10, 2019·Nucleic Acids Research·Ranjit K PrajapatiGeorgiy A Belogurov
Jun 4, 2020·Chemical Biology & Drug Design·Mo-Han HuangXiang-Duan Tan
Jan 17, 2019·Biochemical Society Transactions·Hamed Mosaei, John Harbottle

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.